The effects of hypothalamic microglial activation on ventricular arrhythmias in stress cardiomyopathy.
10.26599/1671-5411.2024.12.002
- Author:
Peng-Qi LIN
1
;
Quan-Wei PEI
1
;
Bin LI
1
;
Jie-Mei YANG
2
;
Li-Na ZOU
1
;
De-Zhan SU
1
;
Jun-Pei ZHANG
1
;
Hong-Peng YIN
1
;
Mbabazi NADINE
1
;
Jun-Jie YANG
1
;
Nevzorova Vera A
3
;
Khan MUSAWIR ABBAS
1
;
Zhao-Lei JIANG
4
;
Jing-Jie LI
1
;
De-Chun YIN
5
Author Information
1. Department of Cardiology, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
2. Department of Echocardiography, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
3. Institute Therapy and Instrumental Diagnostic, Pacific State Medical University, Vladivostok, Russia.
4. Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
5. Department of Geriatrics, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
- Publication Type:Journal Article
- From:
Journal of Geriatric Cardiology
2024;21(12):1119-1132
- CountryChina
- Language:English
-
Abstract:
BACKGROUND:Stress cardiomyopathy (SCM) currently has a high incidence in older adults, and the theories regarding its causes include "catecholamine myocardial toxicity" and "sympathetic hyperactivation". However, the role of the central nervous system in the pathogenesis of SCM remains unknown. We investigated the role of microglia activation in the paraventricular hypothalamic nucleus (PVN) in the development of SCM.
METHODS:An SCM model was created using male Sprague-Dawley (SD) rats, immobilized for 6 h every day for a week. Electrocardiogram, cardiac electrophysiology, and echocardiography examinations were performed to verify the changes in cardiac structure and function in rats with SCM. RNA sequencing was used to explore the changes in the hypothalamus during SCM. In addition, brain and heart tissues were collected to detect microglial activation and sympathetic activity.
RESULTS:The main findings were as follows: (1) immobilization stress successfully induced SCM in SD rats; (2) microglia were significantly activated in the hypothalamus, as evidenced by cytosol thickening, increases in the number of microglial branches, and microglia enriched in the PVN; (3) in SCM, the microglia in the PVN exhibited increased central and peripheral cardiac sympathetic activity and increased the expression of neuroinflammatory factors; and (4) it is possible that inhibiting microglial activation could suppress the sympathetic activity of the central nervous system and heart and increase cardiac electrical stability in SCM rats.
CONCLUSIONS:SCM was induced in SD rats by immobilization stress, acting through the activation of the hypothalamic microglia. The activated microglia were specifically enriched in the PVN, increasing the activity of the central and peripheral sympathetic nervous systems by regulating the expression of neuro-inflammatory factors, mediating dysfunction of the left ventricle, and increasing the susceptibility to ventricular arrhythmias.
